[Prevalence and risk factors of drug induced liver disease: a survey based study in pharmacies]. / Häufigkeit und Risikofaktoren medikamentös-toxischer Leberschäden: eine umfragebasierte Studie in Apotheken.

AIM: The reported incidence of drug-induced liver injury (DILI) ranges from 1 in 10,000 to 1 in 100,000 patients for most drugs, but the true incidence is expected to be much higher. Several risk factors for DILI susceptibility have been suggested, however there is insufficient data to define an individual risk profile. Therefore it was our aim to study the prevalence of DILI and potential risk factors within adult pharmacy customers in Germany. METHODS: We conducted two 6 week-survey studies in 30 pharmacies in 2011 and 2012, respectively, using a newly developed questionnaire comprising questions on demography, (liver) diseases, liver enzyme activities, and drug history. In each study, anonymized questionnaires were presented to non-selected adult customers taking (non-)prescription drugs. RESULTS: Combining the datasets from the 2011 and 2012 surveys, in total 1098 questionnaires were evaluated (mean age 57.7 ±â€Š17.1 years; 62.6 % females, return rate 15.25 %). Overall, 141 individuals (12.8 %) reported elevated liver enzymes due to drugs, in 65 cases (5.9 %) the medication had to be stopped, and 20 customers (1.8 %) reported that they had been admitted to hospital due to DILI. Compared to individuals without adverse hepatic drug reactions (n = 957), the 141 persons with potential DILI presented more often the following risk factors in multivariate analysis: chronic liver disease (14.4 % vs. 2.4 %, odds ratio [OR] 4.2, 95 % confidence interval [CI] 2.0 - 9.0), chronic renal insufficiency (20.0 vs. 6.8 %, OR 2.2, 95 % CI 1.3 - 3.7), diabetes (34 vs. 15.3 %, OR 2.0, 95 % CI 1.3 - 3.2), family history of chronic liver disease (19.9 vs. 7.7 %, OR 2.1, 95 % CI 1.2 - 3.6), and continuous drug intake for more than 5 years (80.9 vs. 59.3 %, OR 2.1, 95 % CI 1.3 - 3.5). CONCLUSION: These studies show an unexpected high prevalence of DILI in pharmacy customers and identify multiple potential risk factors.

[Insulin and proinsulin secretion under contraceptive steroid administration (author's transl)]. / Insulin- und Proinsulin-Sekretion bei Anwendung antikonzeptioneller Steroide

An ivestigation has been performed in 49 women about the influence exerted on the glucose-tolerance, insulin and proinsulin secretion by hormonal contraceptives of different types and compositions. A disturbed dynamics of the insulin secretion with elevated values in the OGTT at two and three hours has been proven at a nearly equal degree using combined preparations (Anacyclin, Eugynon, Neogynon, Mikrogynon) or sequential preparations (Kombiquens, Ovanon). Though there has been interference with the glucose tolerance, the serum proinsulin in the OGTT showed increased levels too. When a combined preparation was applied, the proinsulin values were significantyl higher compared to a sequential type contraceptive. The observed disturbance of the insulin and proinsulin secretion is explained by a decreased sensitivity to insulin in the peripheral fat tissue. The actual dose of the estrogen-gestagen components has no influence on the described changes. Elevated insulin levels are demonstrable already during the first treatment cycle. The degree of the disturbance is independent of the duration of the medicamentous application during the first 6 contraceptive months. After withdrawal of the respective contraceptive steroid the insulin secretion showed nearly normal dynamics during the subseqeunt menstrual cycle.

PIP: An investigation has been performed in 49 women with the influence exerted on the glucose tolerance, insulin and proinsulin secretion by hormonal contraceptives of different types and compositions. Disturbed dynamics of the insulin secretion with elevated values in the OGTT at 2 and 3 hours was proven at a nearly equal degree using combined preparations (Anacyclin, Eugynon, Neogynon, Mikrogynon) or sequential preparations (Kombiquens, Ovanon). Though there was interference with the glucose tolerance, the serum proinsulin in the OGTT showed increased levels, too. When a combined preparation was used, the proinsulin values were significantly higher compared with a sequential type contraceptive. The observed disturbance of the insulin and proinsulin secretion is explained by a decreased sensitivity to insulin in the peripheral fat tissue. The actual dose of the estrogen-gestagen components has no influence on the described changes. Elevated insulin levels are demonstrable during the 1st treatment cycle. The degree of the disturbance is independent of the duration of treatment during the first 6 contraceptive months. After withdrawal of the respective contraceptive steroid the insulin secretion showed nearly normal dynamics during the subsequent menstrual cycle.

[Basal and reactive proinsulin and insulin secretion in overweight women (author's transl)]. / Basale und reaktive Proinsulin-und Insulinsekretion bei Frauen mit Ubergewicht

Serum proinsulin and insulin levels were measured on 55 normal or overweight women before and after oral glucose administration. The proinsulin proportion of basal total insulin was 70% in women of normal weight. With increasing overweight the relation shifted in favour of insulin. After stimulation with glucose, proinsulin levels were significantly raised, analogous to total insulin, but les marked than the latter. The increased total insulin excretion in obesity was, therefore, largely due to insulin and less to proinsulin. The greater the overweight the later maximal insulin levels were reached after oral glucose administration: proinsulin peaks occurred later than insulin peaks. Measurement of areas from single values and corresponding times for proinsulin and insulin, after stimulation, indicated their significant correlation with the degree of overweight. In women of more than 70% overweight (Broca index), reactive proinsulin and insulin excretion decreased again despite an increase in body weight. They had a definitely reduced carbohydrate tolerance. After reduction in body weight previously increased proinsulin levels fell again. The significance of higher proinsulin levels in fasting subjects, which increased after stimulation and with overweight but were in percentage terms less than those of reactive insulin, remains unexplained.